Stereotactic Ablative Radiotherapy (SABR) in inoperable oligometastatic disease from colorectal cancer: a safe and effective approach

Background: To assess the safety and efficacy of Stereotactic Ablative Radiotherapy (SABR) in oligometastatic patients from colorectal cancer. Methods: 82 patients with 1-3 inoperable metastases confined to one organ (liver or lung), were treated with SABR for a total of 112 lesions in an observational study. Prescription dose ranged between 48 and 75Gy in 3 or 4 consecutive fractions. Primary end-points were local control (LC), overall survival (OS) and progression-free survival (PFS). Secondary end-point was toxicity. Results: Median follow-up was 24 months (range 3-47). One, two and three years LC rate was 90%,80% and 75% (85%,75% and 70% for lung and 95%, 90% and 85% for liver metastases; no statistically significance was found). The difference in LC between the subgroup of lesions treated with >= 60 Gy (n = 58) and those irradiated with 3 cm (p 3 toxicity. Conclusions: SABR is a safe and feasible alternative treatment of oligometastatic colorectal liver and lung metastases in patients not amenable to surgery or other ablative treatments

Hypo-fractionated stereotactic radiotherapy alone using volumetric modulated arc therapy for patients with single, large brain metastases unsuitable for surgical resection

BACKGROUND: Hypo-fractionated stereotactic radiotherapy (HSRT) is emerging as a valid treatment option for patients with single, large brain metastases (BMs). We analyzed a set of our patients treated with HSRT. The aim of this study was to evaluate local control (LC), brain distant progression (BDP), toxicity and overall survival (OS). METHODS: From July 2011 to May 2015, 102 patients underwent HSRT consisting of 27Gy/3fractions for lesions 2.1–3 cm and 32Gy/4 fractions for lesions 3.1–5 cm. Local progression was defined as increase of the enhancing abnormality on MRI, and distant progression as new brain metastases outside the irradiated volume. Toxicity in terms of radio-necrosis was assessed using contrast enhanced T1MRI, T2 weighted-MRI and perfusion- MRI. RESULT: The median maximum diameter of BM was 2.9 cm (range 2.1–5 cm), the median gross target volume (GTV) was 16.3 cm(3) and the median planning target volume (PTV) was 33.7 cm(3) The median,1,2-year local control rate was 30 months, 96, 96 %; the median, 1–2-year rate of BDP was 24 months, 12, 24 %; the median,1,2-year OS was 14 months, 69, 33 %. KPS and controlled extracranial disease were associated with significant survival benefit (p <0.01). Brain radio-necrosis occurred in six patients (5.8 %). CONCLUSION: In patients with single, large BMs unsuitable for surgical resection, HSRT is a safe and feasible treatment, with good brain local control and limited toxicity

Synthesis, characterization, and in vitro-in ovo toxicological screening of silibinin fatty acids conjugates as prodrugs with potential biomedical applications

Silibinin (SIL), the most active phytocompound from Silybum marianum (L.), exerts many biological effects but has low stability and bioavailability. To overcome these drawbacks, the current research proposed the synthesis of silibilin oleate (SIL-O) and silibilin linoleate (SIL-L) derivatives as prodrugs with potentially optimized properties for biomedical applications, and the establishment of their in vitro-in ovo safety profiles. The physicochemical characterization of the obtained compounds using density functional theory (DFT) calculations, and Raman and 1H liquid-state nuclear magnetic resonance (NMR) spectroscopy confirmed the formation of SIL-O and SIL-L complexes. Computational predictions revealed that these lipophilic derivatives present a lower drug-likeness score (-29.96 for SIL-O and -23.55 for SIL-L) compared to SIL, but an overall positive drug score (0.07) and no risk for severe adverse effects. SIL-O and SIL-L showed no cytotoxicity or impairment in cell migration at low concentrations, but at the highest concentration (100 µM), they displayed distinct toxicological profiles. SIL-L was more cytotoxic (on cardiomyoblasts - H9c2(2-1), hepatocytes - HepaRG, and keratinocytes - HaCaT) than SIL-O or SIL, significantly inhibiting cell viability (< 60%), altering cellular morphology, reducing cell confluence (< 70%), and inducing prominent apoptotic-like nuclear features. At the concentration of 100 µM, SIL-O presented an irritation score (IS) of 0.61, indicating a lack of irritant effect on the chorioallantoic membrane (CAM), while SIL-L was classified as a slight irritant with an IS of 1.99. These findings outline a more favorable in vitro and in ovo biocompatibility for SIL-O compared to SIL-L, whose applications are dosage-limited due to potential toxicity

Phase II trial of hypofractionated VMAT-based treatment for early stage breast cancer: 2-year toxicity and clinical results

BACKGROUND: To report toxicity and early clinical outcomes of hypofractionated simultaneous integrated boost (SIB) approach with Volumetric Modulated Arc Therapy (VMAT) as adjuvant treatment after breast-conserving surgery. METHODS: Patients presenting early-stage breast cancer were enrolled in a phase II trial. Eligibility criteria: age > 18 years old, invasive cancer or ductal carcinoma in situ (DCIS), Stage I-II (T < 3 cm and N ≤ 3), breast-conserving surgery without oncoplastic reconstruction. Any systemic therapy was allowed in neoadjuvant or adjuvant setting. All patients underwent VMAT-SIB technique to irradiate the whole breast and the tumor bed. Doses to whole breast and surgical bed were 40.5 Gy and 48 Gy, respectively, delivered in 15 fractions over 3 weeks. Acute and late skin toxicities were recorded. Cosmetic outcome was assessed as excellent/good or fair/poor. RESULTS: The present study focused on results of a cohort of 144 patients with a minimum follow-up of 24 months (median 37, range 24–55 months). Median age was 62 years old (range 30–88). All patients had an invasive carcinoma (no patients with DCIS were present in this subset). At one year, the highest reported skin toxicity was G1, in 14 % of the patients; this data dropped to 4 % at the last follow-up, after more than 2 years. Breast pain was recorded in 21.6 % of the patients 6 months after treatment, while it was present in 3.5 % of the patients at the last follow-up, showing a significant improvement with time. Correlation between liponecrosis and boost target volume was found not significant. Breast pain was correlated with breast volume. No pulmonary or cardiological toxicities were recorded. After an early evaluation of clinical outcomes, only one case presented disease relapse, as liver metastases. CONCLUSIONS: The 3-week VMAT-SIB course as adjuvant treatment after breast-conserving surgery showed to be well tolerated and was associated with optimal local control. Long-term follow-up data are needed to assess late toxicity and clinical outcomes